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Pharmaceutical Industry
Published in Roger Cooter, John Pickstone, Medicine in the Twentieth Century, 2020
The German chemical firms were even more innovative than their exploitation of economies of scope might suggest. One of the first new ventures was the production of antitoxins for diphtheria and tetanus. Not only did they pursue new practices — they had to gain expertise in using animals as biological inputs — but they also entered into new networks of relationships including the state and research institutes. With antitoxin manufacture successfully underway, chemical companies, especially Hoechst and Bayer, turned their attention to diseases as targets of industrial innovation. In this they were particularly motivated by Ehrlich’s development of the side-chain theory, receptors and the promise of experimental chemotherapy. Salvarsan, an arsenical compound for the treatment of syphilis, was the major preparation to come out of this practice before 1914.
Basic Pharmaceutical Disciplines
Published in Gregory Higby, Elaine C. Stroud, The History of Pharmacy, 2018
Gregory Higby, Elaine C. Stroud
A lucid account of the pioneering contributions of Paul Ehrlich and John Newport Langley to the development of receptor theory. Addresses the development of Ehrlich’s side-chain theory of immunity, his reluctance to extend this to drug action, and how J. N. Langley’s own work on receptors as an explanation of drug action, together with Ehrlich’s studies on drug resistance, eventually led Ehrlich to postulate his receptor theory of drug action.
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Published in Anton Sebastian, A Dictionary of the History of Medicine, 2018
Side-Chain Theory A few chemotherapeutic agents, such as cinchona, mercury and ipecacuanha, were known before Paul Ehrlich (1854–1915) started working on the side-chain theory, while director of the Institute for Experimental Therapy at Frankfurt in 1898. He proposed that an antigen had two distinct groups ‘haptophore’ and ‘toxophile’, and the side-chains in mammalian cells contained receptors which anchored the haptophores. This combination brought otherwise harmless toxophiles close enough to the cell to poison it. He used this principle to develop a manmade chemotherapeutic agent, tryphan red, which cured infected mice with trypanosomiasis in 1904. This was followed by his development of arsphenamine, or salvarsan, in 1910.
Calcium-dependent, non-apoptotic, large plasma membrane bleb formation in physiologically stimulated mast cells and basophils
Published in Journal of Extracellular Vesicles, 2019
C. Jansen, C Tobita, E. U. Umemoto, J. Starkus, N. M. Rysavy, L. M. N. Shimoda, C. Sung, A.J. Stokes, H Turner
Mast cells are immune cells with very marked and functional membrane rearrangements upon activation. Since the first histological descriptions of mast cell activation in the 1880s, it has been recognized that visible, reversible, membrane derangements are linked to the activation process. Ehrlich’s original descriptions of ‘side chain theory’ included representations of membrane vesicularization on mast cells [8]. Through the seminal EM studies of the Dvorak group in the 1970s and 1980s, to current live-cell fluorescence-based studies, it is clear that mast cells, in addition to the Rho/Rac-mediated membrane ruffling that is common to activating leukocytes, undergo distinctive dynamic membrane changes [9–17]. These are: (1) the formation and release of small (~10 nm diameter) exosomes [18,19], putative intercellular communication structures on which there is an extensive literature and (2) the release of ~50 nm secretory vesicles [20,21]. A third type of membrane rearrangement has been documented in two types of studies in model or primary mast cells – the formation of very large (>1 micron)-diameter membrane protrusions that do not detach. The other instance in which these large structures have been documented is in the enigmatic ‘degranulation channel’ [22] into which the proteoglycan cores of secretory granules (SGs) have been proposed to discharge, followed by the fusion of secretory vesicles into large structures. The formation of apparent degranulation channels has been observed in EM sections of tissue resident and circulating mast cells and basophils [11,23], but their physiological realization, relevance and mechanisms of formation are poorly understood.